IgG autoantibodies against ACE2 in SARS‐CoV‐2 infected patients

Abstract

How frequently autoantibodies against angiotensin‐converting enzyme 2 (ACE2) occur in patients infected by SARS‐CoV‐2 is understudied and limited to investigations on a small sample size. The presence of these antibodies may contribute to the long‐lasting effects of COVID‐19 observed in some individuals, particularly if IgG‐class antibodies would emerge in patients. This study assessed the prevalence of IgG autoantibodies against ACE2 in 1139 patients infected with SARS‐CoV‐2 and examined their relationship with severity, demographic characteristics, and status of vaccination against influenza. The overall prevalence of anti‐ACE IgG antibodies in our cohort was 1.5%. Most of these individuals were men (76.5%) and underwent mild COVID‐19, but some severe and asymptomatic cases were also observed. Patients with severe infection had twofold higher titers than mild and asymptomatic cases. Age, comorbidities, and influenza vaccination status were not related to antibody prevalence. The prevalence of IgG anti‐SARS‐CoV‐2 antibodies (against nucleocapsid protein and S2 subunit, but not against receptor‐binding domain) was higher in the subset with ACE2 autoantibodies. Further research is required to understand the potential spectrum and duration of effects of IgG autoantibodies against ACE2 in patients after SARS‐CoV‐2 infection, particularly concerning long COVID‐19.

Overview of autoantibodies in COVID‐19 convalescents

“…There are also reports on the autoantibodies against ACE2 that serves as the receptor for cellular entry of SARS‐CoV‐2 59,74,75 . At the same time, ACE2 plays a role in the renin−angiotensin hormone system by transforming angiotensin II into protective angiotensin (1−7) and regulating blood volume, hemato‐ and erythropoiesis, apart from its functions in immunity and stem cell maintenance 76 .…”

“…58,78 However, one study reported the seroprevalence of IgG anti-ACE2 antibodies in 1.5% of subjects, mostly men and patients who underwent mild COVID-19 (although they were sporadically also found in severe and asymptomatic cases). 59 It can be suggested that such antibodies may be produced as a part of immune mechanisms leading to the suppression of the viral spread or represent so-called homebodies that recognize the binding partner of the original viral protein. 59,79 Although anti-ACE2 antibodies can be detrimental to cardiovascular function as well as a variety of organs causing tissue inflammation, 80,81 it should be noted that their expected seroprevalence, unrelated to COVID-19, is not known, particularly in the case of IgG antibodies.…”

“…The studies predominantly show that SARS‐CoV‐2 can lead to the emergence of functional IgM antibodies against ACE2 (Table 2), with one study failing to demonstrate their class switch to IgG 58,78 . However, one study reported the seroprevalence of IgG anti‐ACE2 antibodies in 1.5% of subjects, mostly men and patients who underwent mild COVID‐19 (although they were sporadically also found in severe and asymptomatic cases) 59 . It can be suggested that such antibodies may be produced as a part of immune mechanisms leading to the suppression of the viral spread or represent so‐called homebodies that recognize the binding partner of the original viral protein 59,79 .…”

“…73 There are also reports on the autoantibodies against ACE2 that serves as the receptor for cellular entry of SARS-CoV-2. 59,74,75 At the same time, ACE2 plays a role in the renin−angiotensin hormone system by transforming angiotensin II into protective angiotensin (1−7) and regulating blood volume, hemato-and erythropoiesis, apart from its functions in immunity and stem cell maintenance. 76 Therefore, autoantibodies against ACE2 can be highly detrimental and affect numerous physiological processes, particularly if one considers its wide expression encompassing cardiomyocytes, the brain, intestines, kidneys, and the male reproductive tract.…”

COVID-19, post-acute COVID-19 syndrome (PACS, “long COVID”) and post-COVID-19 vaccination syndrome (PCVS, “post-COVIDvac-syndrome”): Similarities and differences

“…Autoantibodies were detected during the acute phase of COVID-19 [316] , [317] , [318] , [319] , [320] , [321] , [322] , [323] , [324] , [325] , [326] , [327] , [328] , [329] , [330] , [331] , [332] , [333] , months afterwards (predicting PACS symptoms) [334] , [335] , in PACS [336] , [337] , [338] , [339] , [340] , and in PCVS [295] , [298] , [341] , [342] , [343] , [344] , [345] , [346] , [347] , [348] , [349] , [350] , [351] , [352] , [353] , [354] , [355] , [356] , [357] , [358] , [359] , [360] , [361] , [362] , [363] , [364] , [365] . In the absence of PCVS after COVID-19 vaccination, autoantibodies are generally not present [366] , [367] , [368] .…”